Significant advances have been made in medical anatomical imaging over the past 25 years. More recently, there has been increased interest in small animal biological imaging research based on the increasing understanding of various molecular and genetic signals in tumor cells in vitro and in vivo. These initiatives have focused primarily on therapeutic research with drugs and other systemic agents, somewhat ironically, overlooking radiation therapy. The addition of biological imaging information to radiation therapy will have a major impact on the management and evaluation of treatment. Unfortunately, despite the interest in biological imaging research, animal radiation research methodology lags far behind clinical practices. Advanced techniques such as conformal, intensity modulated radiation therapy (IMRT) is increasingly becoming routine in human clinics, and has led to a shift in the clinical paradigm of the uniform dose delivery towards non-uniform dose delivery, particularly to the critical organs. The advent of new image guidance methods for short course radiation treatment will yet lead to the delivery of dose distributions of even greater nonuniformity. Regrettably, present laboratory research equipment prohibits testing of these paradigms in animal models. As a consequence, the advanced treatment technologies are applied clinically without any guidance from small animal radiation experimentation to evaluate efficacy in a preclinical setting. In this proposal we request funding for the de novo construction, testing and evaluation of an image guided small animal radiation research platform (SARRP) that will accurately deliver complex ionizing radiation dose distributions in small animal tumor model systems, mice, rats and rabbits. Specifically we propose 1) the construction of a gantry system containing three kilovoltage (kV) radiation sources that will have energy deposition resolution of about 1mm and on-board cone beam CT imaging resolution of about 0.5 mm; 2) the development of dosimetric and treatment planning methodologies that parallel that for human treatment. Finally (3) the third specific aim is to develop methods of precise animal setups and to validate the imaging and irradiation capabilities of the system for accurate delivery of localized dose distributions in small animals. The research requires integration of expertise in mechanical engineering, x-ray optics and radiation dosimetry physics. The collaborative efforts are best coordinated in a Bioengineering Research Partnership (BRP). An Oversight Group is formed to evaluate the progress of the BRP, and to help identify opportunities and hypotheses for future research.